Norepinephrine-mediated suppression of phagocytosis by wound neutrophils.
BACKGROUND
The systemic response to injury is characterized by massive release of norepinephrine (NE) into the circulation as a result of global sympathetic activation. Multiple authors have demonstrated NE-mediated alterations in migration of circulating neutrophils to wounds. We hypothesized that NE further alters wound neutrophil phagocytic function through adrenergic signaling pathways.


METHODS
A standard subcutaneous sponge wound model was used. Murine wound neutrophils were harvested at 24 and 120 h after injury and treated with physiological (10(-9) M) and pharmacologic (10(-6) M) doses of NE. Phagocytosis of green fluorescent protein-labeled Escherichia coli was assayed by flow cytometry. The signaling pathways mediating NE modulation of phagocytosis by wound neutrophils were defined by pharmacologic manipulation of alpha- and beta-adrenoreceptors and protein kinase A.


RESULTS
Pharmacologic-dose NE, but not-physiological-dose NE, suppressed the phagocytic efficiency of 120-h wound neutrophils. This alteration in phagocytic efficiency appears to be mediated through alpha- and beta- adrenoreceptors and downstream protein kinase A. Phagocytosis by 24-h wound neutrophils was not impacted by NE treatment.


CONCLUSIONS
The present study is the first to demonstrate NE-mediated alterations in the process of phagocytosis by wound neutrophils. We conclude that NE plays a temporally and dose-defined immunomodulatory role in cutaneous wound healing through alterations in phagocytosis by wound neutrophils and may represent a target for therapeutic manipulation of the innate immune response.
Gosain
Ankush
A
Burn and Shock Trauma Institute, Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, Illinois, USA.
Gamelli
Richard L
RL
DiPietro
Luisa A
LA
D000818:Animals; D004926:Escherichia coli / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D010587:Phagocytosis / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology; D014947:Wounds and Injuries / Q000503:physiopathology*
D049452:Green Fluorescent Proteins; D009638:Norepinephrine